Ion capture in helium droplets: formation of cold ion-neutral clusters

Superfluid helium nanodroplets are used to cool ions and form ion-neutral clusters at a temperature of 0.37 K. A desolvation technique was developed that allowed for the study of captured ions by mass spectrometry. From the mass spectrometry results it was determined that helium droplets may successfully capture sodium cations with kinetic energy of ~200 eV. Clusters of the neutral molecules H2O, N2, and HCN with Na+ were observed. Based on binding strength considerations, it is argued that the desolvation process imparts little energy into the ion-neutral clusters, avoiding dissociation. This result leads to the conclusion that ion-neutral clusters are formed within the droplet prior to desolvation, indicating that the helium snowball that is assumed to form around Na+ does not prevent ion-neutral cluster formation. This conclusion is supported by ab initio calculations, the results of which indicate the presence of barrierless pathways for neutral molecule insertion into the helium snowball surrounding Na+. The process of ion capture by helium droplets was studied by comparison of measured ion-doped droplet size distributions to known pre-ion capture droplet size distributions. The measured ion-doped droplet size distributions were affected by nozzle temperature, ion kinetic energy, and ion mass. These factors primarily affect two parameters of the ion-doped droplet size distribution, the minimum droplet size threshold, Nthr, and the droplet size at maximum signal intensity, Nmax. The effects of the studied factors on the measured distributions cannot be explained in terms of currently accepted droplet cooling mechanisms. Analysis of the results suggests that droplet doping efficiency can be improved in several ways, including a higher flux of lower-energy ions. An apparatus for the production and focusing of alkali cations at high fluxes and low energies is described. This apparatus was able to produce higher ion currents at lower kinetic energies than previous ion sources

Heritability and Artificial Selection on Ambulatory Dispersal Distance in Tetranychus urticae: Effects of Density and Maternal Effects

Dispersal distance is understudied although the evolution of dispersal distance affects the distribution of genetic diversity through space. Using the two-spotted spider mite, Tetranychus urticae, we tested the conditions under which dispersal distance could evolve. To this aim, we performed artificial selection based on dispersal distance by choosing 40 individuals (out of 150) that settled furthest from the home patch (high dispersal, HDIS) and 40 individuals that remained close to the home patch (low dispersal, LDIS) with three replicates per treatment. We did not observe a response to selection nor a difference between treatments in life-history traits (fecundity, survival, longevity, and sex-ratio) after ten generations of selection. However, we show that heritability for dispersal distance depends on density. Heritability for dispersal distance was low and non-significant when using the same density as the artificial selection experiments while heritability becomes significant at a lower density. Furthermore, we show that maternal effects may have influenced the dispersal behaviour of the mites. Our results suggest primarily that selection did not work because high density and maternal effects induced phenotypic plasticity for dispersal distance. Density and maternal effects may affect the evolution of dispersal distance and should be incorporated into future theoretical and empirical studies

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Management of peripheral arterial disease in the elderly: focus on cilostazol

Travis M Falconer1, John W Eikelboom2, Graeme J Hankey3, Paul E Norman11School of Surgery, University of Western Australia, Fremantle Hospital, Western Australia; 2Department of Medicine, McMaster University, Hamilton, Canada; 3Department of Neurology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western AustraliaAbstract: Symptomatic and asymptomatic peripheral arterial disease (PAD) is a common problem in the elderly. The management of PAD includes the prevention of cardiovascular events and relief of symptoms – most commonly intermittent claudication (IC). Both require treatment of the causes and consequences of atherothrombosis, but some strategies are more effective for prevention of cardiovascular events and others are more effective for the relief of symptoms. Priorities for the prevention of cardiovascular events include smoking cessation, exercise, antiplatelet therapy, and the treatment of dyslipidemia, hypertension, and diabetes. Walking time and ability are improved by exercise. The benefit of numerous drugs in the treatment of IC has been assessed. The results have generally been disappointing, but there is some evidence that statins and cilostazol (an inhibitor of phosphodiesterase 3) are of benefit. Meta-analyses suggest that cilostazol increases maximum walking distance by 40%–50% and improves other objective measures of walking. The safety profile of cilostazol in patients with PAD appears to be acceptable although the mechanism for its effect on IC is unclear. In addition to risk factor management, treatment with cilostazol should be considered in patients with disabling IC.Keywords: peripheral arterial disease, intermittent claudication, risk factors, cilostazo

Phenotypic and genomic plasticity of alternative male reproductive tactics in sailfin mollies

A major goal of modern evolutionary biology is to understand the causes and consequences of phenotypic plasticity, the ability of a single genotype to produce multiple phenotypes in response to variable environments. While ecological and quantitative genetic studies have evaluated models of the evol- ution of adaptive plasticity, some long-standing questions about plasticity require more mechanistic approaches. Here, we address two of those questions: does plasticity facilitate adaptive evolution? And do physiological costs place limits on plasticity? We examine these questions by comparing genetically and plastically regulated behavioural variation in sailfin mollies (Poecilia latipinna), which exhibit striking variation in plasticity for male mating behav- iour. In this species, some genotypes respond plastically to a change in the social environment by switching between primarily courting and primarily sneaking behaviour. In contrast, other genotypes have fixed mating strategies (either courting or sneaking) and do not display plasticity. We found that gen- etic and plastic variation in behaviour were accompanied by partially, but not completely overlapping changes in brain gene expression, in partial support of models that predict that plasticity can facilitate adaptive evolution. We also found that behavioural plasticity was accompanied by broader and more robust changes in brain gene expression, suggesting a substantial physiological cost to plasticity. We also observed that sneaking behaviour, but not courting, was associated with upregulation of genes involved in learning and memory, suggesting that sneaking is more cognitively demanding than courtship